A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Last updated: May 13, 2025
Sponsor: Mirati Therapeutics Inc.
Overall Status: Active - Recruiting

Phase

3

Condition

N/A

Treatment

Pemetrexed

Pembrolizumab

Adagrasib

Clinical Study ID

NCT06875310
CA239-0004
CA2390004
  • Ages > 18
  • All Genders

Study Summary

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of non-squamous NSCLC withevidence of KRAS G12C mutation via tumor tissue and/or circulating tumordeoxyribonucleic acid (ctDNA).

  • Locally advanced or metastatic disease.

  • Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI)per RECIST v1.1 criteria of at least 1 lesion.

  • No prior systemic anti-cancer therapy given for advanced or metastatic disease.

  • Not a candidate for definitive therapy (eg, chemoradiation or complete surgicalresection).

  • Participants with brain metastases are eligible for enrollment, including those withuntreated brain metastases. Brain metastases must be asymptomatic and not in need ofimmediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.

  • Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay,Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.

Exclusion

Exclusion Criteria:

  • Participants with an active, known, prior documented, or suspected autoimmune orinflammatory disease.

  • Uncontrolled or significant cardiovascular conditions within 6 months prior toenrollment.

  • Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.

  • Ongoing treatment with concomitant medication known to cause prolonged QTc intervaland that cannot be switched to alternative treatment prior to study entry.

  • Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.

  • Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation or studydrug administration.

  • Other protocol-defined Inclusion/Exclusion criteria apply.

Study Design

Total Participants: 630
Treatment Group(s): 6
Primary Treatment: Pemetrexed
Phase: 3
Study Start date:
April 24, 2025
Estimated Completion Date:
April 30, 2032

Connect with a study center

  • Local Institution - 0575

    Ciudad Autónoma de Buenos Aires, Buenos Aires C1426ANZ
    Argentina

    Site Not Available

  • IDIM - Instituto de Investigaciones Metabólicas

    Ciudad de Buenos Aires, Buenos Aires C1012AAR
    Argentina

    Active - Recruiting

  • Local Institution - 0570

    Ciudad de Buenos Aires, Buenos Aires C1012AAR
    Argentina

    Site Not Available

  • Local Institution - 0584

    Pilar, Buenos Aires 1629
    Argentina

    Site Not Available

  • Hospital Italiano de Buenos Aires

    ABB, Ciudad Autónoma De Buenos Aires C1199ABB
    Argentina

    Active - Recruiting

  • Local Institution - 0576

    ABB, Ciudad Autónoma De Buenos Aires C1199ABB
    Argentina

    Site Not Available

  • Local Institution - 0571

    Buenos Aires, Ciudad Autónoma De Buenos Aires C1417DTB
    Argentina

    Site Not Available

  • Local Institution - 0573

    Caba, Ciudad Autónoma De Buenos Aires C1430EGF
    Argentina

    Site Not Available

  • Local Institution - 0569

    Río Cuarto, Córdoba X5800ALB
    Argentina

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  • Local Institution - 0595

    Rosario, Santa Fe 2000
    Argentina

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    Canberra, Australian Capital Territory 2605
    Australia

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  • Local Institution - 0212

    North Tamworth, New South Wales 2340
    Australia

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  • Tamworth Hospital

    North Tamworth, New South Wales 2340
    Australia

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  • Local Institution - 0128

    Orange, New South Wales 2800
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    Brisbane, Queensland 4102
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    Elizabeth Vale, South Australia 5112
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  • Lyell McEwin Hospital

    Elizabeth Vale, South Australia 5112
    Australia

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  • Frankston Hospital

    Frankston, Victoria 3199
    Australia

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    Melbourne, Victoria 3076
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    Traralgon, Victoria 3844
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    Joondalup, Western Australia 6027
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    Sao Paulo, São Paulo 01509-010
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    São Carlos, São Paulo 13561-130
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    Mulhouse, Alsace 68100
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    Caen, Calvados 14076
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    Angers, Maine-et-Loire 49933
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    Osaka, 534-0021
    Japan

    Site Not Available

  • Local Institution - 0309

    Osaka, 541-8567
    Japan

    Site Not Available

  • Local Institution - 0163

    Cheongju-si, Chungcheongbuk-do [Chungbuk] 28644
    Korea, Republic of

    Site Not Available

  • Local Institution - 0227

    Namdong-gu, Incheon-gwangyeoksi [Incheon] 21565
    Korea, Republic of

    Site Not Available

  • Local Institution - 0211

    Yangsan, Kyǒngsangnam-do 50612
    Korea, Republic of

    Site Not Available

  • Local Institution - 0186

    Busan, Pusan-Kwangyǒkshi 49241
    Korea, Republic of

    Site Not Available

  • Local Institution - 0146

    Seoul, Seoul-teukbyeolsi [Seoul] 08308
    Korea, Republic of

    Site Not Available

  • Local Institution - 0165

    Seoul, Seoul-teukbyeolsi [Seoul] 03722
    Korea, Republic of

    Site Not Available

  • Local Institution - 0228

    Seoul, Seoul-teukbyeolsi [Seoul] 05030
    Korea, Republic of

    Site Not Available

  • Local Institution - 0248

    Seoul, Seoul-teukbyeolsi [Seoul] 06591
    Korea, Republic of

    Site Not Available

  • Local Institution - 0583

    Saltillo, Coahuila 25279
    Mexico

    Site Not Available

  • Local Institution - 0176

    Mexico City, DIF 11510
    Mexico

    Site Not Available

  • Local Institution - 0579

    Pachuca, Hidalgo 42000
    Mexico

    Site Not Available

  • Local Institution - 0174

    Guadalajara, Jalisco 44630
    Mexico

    Site Not Available

  • Local Institution - 0178

    Guadalajara, Jalisco 44280
    Mexico

    Site Not Available

  • Local Institution - 0591

    Monterrey, Nuevo León 64040
    Mexico

    Site Not Available

  • Local Institution - 0175

    Chihuahua, 31217
    Mexico

    Site Not Available

  • Local Institution - 0181

    Puebla, 72424
    Mexico

    Site Not Available

  • Local Institution - 0638

    Puebla, 72530
    Mexico

    Site Not Available

  • Local Institution - 0180

    Veracruz, 91900
    Mexico

    Site Not Available

  • Local Institution - 0615

    Maastricht, Limburg 6229 HX
    Netherlands

    Site Not Available

  • Local Institution - 0594

    Amsterdam, Noord-Holland 1066 CX
    Netherlands

    Site Not Available

  • Local Institution - 0205

    Wrocław, Dolnośląskie 53-439
    Poland

    Site Not Available

  • Local Institution - 0080

    Lublin, Lubelskie 20-954
    Poland

    Site Not Available

  • Local Institution - 0206

    Gorlice, Małopolskie 38-300
    Poland

    Site Not Available

  • Local Institution - 0079

    Kraków, Małopolskie 30-727
    Poland

    Site Not Available

  • Local Institution - 0077

    Prabuty, Pomorskie 82-550
    Poland

    Site Not Available

  • Local Institution - 0209

    Poznan, Wielkopolskie 60-693
    Poland

    Site Not Available

  • Local Institution - 0076

    Bydgoszcz, 85796
    Poland

    Site Not Available

  • Local Institution - 0078

    Katowice, 40-519
    Poland

    Site Not Available

  • Local Institution - 0509

    Lisbon, Lisboa 1099-023
    Portugal

    Site Not Available

  • Local Institution - 0510

    Coimbra, 3000-075
    Portugal

    Site Not Available

  • Local Institution - 0553

    Porto, 4099-001
    Portugal

    Site Not Available

  • Local Institution - 0261

    Bucharest, București 022338
    Romania

    Site Not Available

  • Local Institution - 0272

    Bucharest, București 013812
    Romania

    Site Not Available

  • Local Institution - 0276

    Cluj-Napoca, Cluj 400015
    Romania

    Site Not Available

  • Local Institution - 0268

    Florești, Cluj 407280
    Romania

    Site Not Available

  • Local Institution - 0274

    Constanta, Constanța 900591
    Romania

    Site Not Available

  • Local Institution - 0275

    Ovidiu, Constanța 905900
    Romania

    Site Not Available

  • Local Institution - 0271

    Craiova, Dolj 200542
    Romania

    Site Not Available

  • Local Institution - 0269

    Ploiești, Prahova 100337
    Romania

    Site Not Available

  • Local Institution - 0270

    Cluj, 400015
    Romania

    Site Not Available

  • Local Institution - 0273

    Cluj, 400015
    Romania

    Site Not Available

  • Local Institution - 0590

    Constanța, 900591
    Romania

    Site Not Available

  • Local Institution - 0260

    Iași, 700483
    Romania

    Site Not Available

  • Local Institution - 0266

    Iași, 700106
    Romania

    Site Not Available

  • Local Institution - 0592

    Timișoara, 300239
    Romania

    Site Not Available

  • Local Institution - 0614

    Jeddah, Makkah Al Mukarramah 23433
    Saudi Arabia

    Site Not Available

  • Local Institution - 0562

    Riyadh, 12713
    Saudi Arabia

    Site Not Available

  • Local Institution - 0602

    Riyadh, 11426
    Saudi Arabia

    Site Not Available

  • Local Institution - 0499

    A Coruña, A Coruña [La Coruña] 15006
    Spain

    Site Not Available

  • Local Institution - 0506

    Santiago de Compostela, A Coruña [La Coruña] 15706
    Spain

    Site Not Available

  • Local Institution - 0501

    Barcelona, Barcelona [Barcelona] 08035
    Spain

    Site Not Available

  • Local Institution - 0497

    Hospitalet, Barcelona [Barcelona] 08907
    Spain

    Site Not Available

  • Local Institution - 0505

    Barcelona, Catalunya [Cataluña] 08036
    Spain

    Site Not Available

  • Local Institution - 0508

    Palma, Illes Balears [Islas Baleares] 07198
    Spain

    Site Not Available

  • Local Institution - 0496

    Madrid, Madrid, Comunidad De 28041
    Spain

    Site Not Available

  • Local Institution - 0500

    Madrid, Madrid, Comunidad De 28009
    Spain

    Site Not Available

  • Local Institution - 0503

    Madrid, Madrid, Comunidad De 28034
    Spain

    Site Not Available

  • Local Institution - 0498

    Majadahonda, Madrid, Comunidad De 28222
    Spain

    Site Not Available

  • Local Institution - 0669

    Pontevedra, Pontevedra [Pontevedra] 36312
    Spain

    Site Not Available

  • Local Institution - 0640

    Valencia, València 46015
    Spain

    Site Not Available

  • Local Institution - 0504

    Madrid, 28040
    Spain

    Site Not Available

  • Local Institution - 0502

    Málaga, 29011
    Spain

    Site Not Available

  • Local Institution - 0507

    Sevilla, 41013
    Spain

    Site Not Available

  • Local Institution - 0495

    València, 46026
    Spain

    Site Not Available

  • Local Institution - 0538

    st.Gallen, Sankt Gallen 9007
    Switzerland

    Site Not Available

  • Local Institution - 0536

    Münsterlingen, 8596
    Switzerland

    Site Not Available

  • Chi Mei Hospital - Liouying Branch

    Tainan City, Tainan 73657
    Taiwan

    Active - Recruiting

  • Local Institution - 0341

    Tainan City, Tainan 73657
    Taiwan

    Site Not Available

  • Local Institution - 0631

    Taipei City, Taipei 114
    Taiwan

    Site Not Available

  • Local Institution - 0337

    New Taipei, 235
    Taiwan

    Site Not Available

  • Taipei Medical University Shuang Ho Hospital

    New Taipei, 235
    Taiwan

    Active - Recruiting

  • Local Institution - 0335

    Tainan, 704
    Taiwan

    Site Not Available

  • Local Institution - 0331

    Taipei, 10002
    Taiwan

    Site Not Available

  • National Taiwan University Hospital

    Taipei, 10002
    Taiwan

    Active - Recruiting

  • Local Institution - 0565

    Muang, Khon Kaen 40002
    Thailand

    Site Not Available

  • Local Institution - 0563

    Bangkok, Krung Thep Maha Nakhon 10330
    Thailand

    Site Not Available

  • Local Institution - 0564

    Hatyai, Songkhla 90110
    Thailand

    Site Not Available

  • Local Institution - 0548

    Stanbul, İstanbul 34214
    Turkey

    Site Not Available

  • Local Institution - 0199

    Izmir, Karsiyaka, İzmir 009035575
    Turkey

    Site Not Available

  • Local Institution - 0197

    Adana, 01250
    Turkey

    Site Not Available

  • Local Institution - 0194

    Ankara, 0
    Turkey

    Site Not Available

  • Local Institution - 0198

    Ankara, 06800
    Turkey

    Site Not Available

  • Local Institution - 0201

    Ankara, 06230
    Turkey

    Site Not Available

  • Local Institution - 0549

    Istanbul, 34722
    Turkey

    Site Not Available

  • Local Institution - 0200

    Izmir, 35100
    Turkey

    Site Not Available

  • Local Institution - 0550

    Malatya, 44280
    Turkey

    Site Not Available

  • Local Institution - 0088

    London, London, City Of NW1 2PG
    United Kingdom

    Site Not Available

  • Local Institution - 0091

    London, London, City Of SE1 9RT
    United Kingdom

    Site Not Available

  • University College London Hospital

    London, London, City Of NW1 2PG
    United Kingdom

    Active - Recruiting

  • Local Institution - 0092

    Birmingham, B9 5SS
    United Kingdom

    Site Not Available

  • Local Institution - 0090

    Guildford, GU2 7XX
    United Kingdom

    Site Not Available

  • Local Institution - 0545

    Guildford, GU2 7XX
    United Kingdom

    Site Not Available

  • Local Institution - 0093

    Manchester, M20 4BX
    United Kingdom

    Site Not Available

  • Local Institution - 0347

    Birmingham, Alabama 35294-3300
    United States

    Site Not Available

  • Local Institution - 0581

    Fullerton, California 92835
    United States

    Site Not Available

  • Local Institution - 0202

    Long Beach, California 90805
    United States

    Site Not Available

  • Local Institution - 0643

    Newport Beach, California 92663
    United States

    Site Not Available

  • Local Institution - 0666

    Orange, California 92868
    United States

    Site Not Available

  • Local Institution - 0623

    Santa Barbara, California 93105
    United States

    Site Not Available

  • Local Institution - 0442

    Denver, Colorado 80206
    United States

    Site Not Available

  • Local Institution - 0651

    Gainesville, Florida 32610
    United States

    Site Not Available

  • Local Institution - 0621

    Palm Bay, Florida 32901
    United States

    Site Not Available

  • Local Institution - 0377

    Tamarac, Florida 33321
    United States

    Site Not Available

  • Local Institution - 0647

    Tampa, Florida 33612
    United States

    Site Not Available

  • Local Institution - 0392

    Fort Eisenhower, Georgia 30905
    United States

    Site Not Available

  • Local Institution - 0031

    Marietta, Georgia 30060
    United States

    Site Not Available

  • Local Institution - 0665

    Arlington Heights, Illinois 60005
    United States

    Site Not Available

  • Local Institution - 0423

    Munster, Indiana 46321
    United States

    Site Not Available

  • Local Institution - 0366

    Edgewood, Kentucky 41017
    United States

    Site Not Available

  • Local Institution - 0566

    Louisville, Kentucky 40202
    United States

    Site Not Available

  • Local Institution - 0644

    Shreveport, Louisiana 71103
    United States

    Site Not Available

  • Local Institution - 0385

    Columbia, Maryland 21044
    United States

    Site Not Available

  • Local Institution - 0019

    Boston, Massachusetts 02215
    United States

    Site Not Available

  • Local Institution - 0437

    Worcester, Massachusetts 01655
    United States

    Site Not Available

  • Local Institution - 0618

    White Plains, New York 10601
    United States

    Site Not Available

  • Local Institution - 0624

    Asheville, North Carolina 28806
    United States

    Site Not Available

  • Local Institution - 0620

    Columbus, Ohio 43219
    United States

    Site Not Available

  • Local Institution - 0657

    York, Pennsylvania 17403
    United States

    Site Not Available

  • Local Institution - 0658

    Greenville, South Carolina 29607
    United States

    Site Not Available

  • Local Institution - 0051

    Austin, Texas 78731
    United States

    Site Not Available

  • Local Institution - 0652

    Laredo, Texas 78041
    United States

    Site Not Available

  • Local Institution - 0622

    San Antonio, Texas 78217
    United States

    Site Not Available

  • Local Institution - 0332

    Seattle, Washington 98101
    United States

    Site Not Available

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